Proteus mirabilis

A sampling of research in the last decade that points strongly to a correlation between the upper urinary tract infection, Proteus mirabilis, as both a trigger for and the progression of seropositive rheumatoid arthritis (RA).

The link between Proteus mirabilis, environmental factors and autoantibodies in rheumatoid arthritis. Clin Exp Rheumatol. 2017 May 8.

Researchers point to Proteus mirabilis as being a major microbial cause of rheumatoid arthritis (RA), as evidenced by the role this infection plays in autoantibody production commonly associated with RA, such as rheumatoid factors (RF) and anti-citrullinated peptide antibodies (anti-CCP).  Study authors state the most likely mechanism by which RA is caused is molecular mimicry, where Proteus antigens, sharing homologous sequences with certain self-antigens, will cross-react when these are present in synovial tissues and that novel treatment strategies for treating RA may arise from an understanding of this microbe-host interplay.

Greek rheumatoid arthritis patients have elevated levels of antibodies against antigens from Proteus mirabilis. Clin Rheumatol. 2017 Mar;36(3):527-535.

In a study of 63 rheumatoid arthritis (RA) patients and 38 healthy controls for Proteus mirabilis infection, Greek researchers found a significant correlation between rheumatoid factors (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) with anti-peptide antibodies in those testing positive for this infection. Although cross-reacting antigenic etiopes were found in lower percentages, Greek RA patients with elevated antibodies against Proteus mirabilis were comparable to results found in studies of RA patients in Northern Europe. The authors conclude that Proteus mirabilis infection leads to inflammation and joint damage in RA by the mechanism of molecular mimicry.

Rheumatoid arthritis is caused by a Proteus urinary tract infection. APMIS. 2014 May;122(5):363-8.

British researchers at the Analytical Sciences Group of King’s College, London, UK, state that genetic, molecular and biological studies undertaken by 67 countries indicate that Proteus mirabilis, an infection of the upper urinary tract, is a major causative microbe of rheumatoid arthritis (RA) and that its amino acid sequences explain the early appearance of anti-citrullinated peptide auto-antibodies (anti-CCP). It is the recommendation of these researchers that RA patients are, “…treated early with anti-Proteus antibiotics as well as biological agents to avoid irreversible joint damages.”

The presence of anti-LPS antibodies and human serum activity against Proteus mirabilis S/R forms in correlation with TLR4 (Thr399Ile) gene polymorphism in rheumatoid arthritis. Clin Biochem. 2012 Nov;45(16-17):1374-82.

Polish researchers hypothesize that Proteus mirabilis, a causative infection of urinary tract infections, is also involved in the immunologic response of rheumatoid arthritis (RA).

Distinct bacterial colonization patterns of Escherichia coli subtypes associate with rheumatoid factor status in early inflammatory arthritis. Rheumatology (Oxford). 2010 Jul;49(7):1311-6.

Canadian researchers assert that Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae, have all been correlated with rheumatoid arthritis (RA) disease pathogenesis. This study ties specific urinary or intestinal bacterial sub-types with either seropositive and seronegative rheumatoid factor (RF).

Rheumatoid arthritis, Proteus, anti-CCP antibodies and Karl Popper. Autoimmun Rev. 2010 Feb;9(4):216-23.

British researchers at King’s College, London, discuss the Karl Popper sequencing rationale in respect to Proteus mirabilis infection in rheumatoid arthritis (RA), establishing this infection as a major causative agent for the production of anti-cycline citrullinated peptides (anti-CCP) auto-antibodies, which is used for both diagnostics and prognosis in RA. In conclusion, these study authors state that, “The ten Popper sequences establish that RA is most probably caused by Proteus upper urinary tract infections, which can possibly be treated with anti-Proteus therapy.”

Human complement activation by smooth and rough Proteus mirabilis lipopolysaccharides. Arch Immunol Ther Exp (Warsz). 2009 Sep-Oct;57(5):383-91.

Swedish researchers studied Proteus mirabilis and it’s molecular activation pathways in the human complement system. These researchers assert the important role that this upper urinary tract infection plays in rheumatoid arthritis and its measurable presence in blood.

Rheumatoid arthritis patients have elevated antibodies to cross-reactive and non cross-reactive antigens from Proteus microbes. Clin Exp Rheumatol. 2007 Mar-Apr;25(2):259-67.

Researchers at the School of Biomedical and Health Sciences, Kings College London, discuss the leading role of Proteus mirabilis in rheumatoid arthritis (RA) etiopathogenesis, which remains controversial with rheumatologists who state it is a secondary phenomenon and the result of cross-reactivity between the bacteria and self-antigens. To shed light on this association, these researchers conducted a controlled study of 70 RA patients and concluded that Proteus mirabilis etiopes displayed both cross-reactive and non cross-reactive actions with human tissue antigens, which enhanced tissue reactivity in RA patients. Additionally, they found that serum levels of both anti-peptide antibodies and biochemical markers for disease activity were indicators of response to the infection and its damaging cytotoxic effects on joint tissues during the course of RA disease progression.

Rheumatoid arthritis is linked to Proteus–the evidence. Clin Rheumatol. 2007 Jul;26(7):1036-43. Epub 2007 Jan 6.

British researchers state there is extensive evidence-based medicine pointing to the upper urinary tract infection, Proteus mirabilis, as being a major player in the cause of progression of rheumatoid arthritis (RA). They suggest treatment with targeted antibiotics and dietary measures as a novel therapeutic protocol to be used together with current RA treatments and call for studies to establish the therapeutic benefit of antimicrobial protocols with this microbe-disease association.

Rheumatoid arthritis is an autoimmune disease triggered by Proteus urinary tract infection. Clin Dev Immunol. 2006 Mar;13(1):41-8.

British researchers propose that urinary tract infections, caused by the infection Proteus mirabilis, is a major trigger for and cause of rheumatoid arthritis (RA) progression due molecular mimicry that leads to cross-reactivity with the pathogen and its antigenic substances signaling an immunologic auto-antibody response. The authors recommend antimicrobial treatment, using antibiotics, a vegetarian diet, and plenty of water and fruit juice (e.g. cranberry juice), alongside contemporary rheumatologic treatments.

Elevated levels of IgM and IgA antibodies to Proteus mirabilis and IgM antibodies to Escherichia coli are associated with early rheumatoid factor (RF)-positive rheumatoid arthritis. Rheumatology (Oxford). 2005 Nov;44(11):1433-41.

Based on prior research findings, linking Proteus mirabilis infection to patients with established rheumatoid arthritis (RA), Canadian researchers led this study with a focus on newly diagnosed cases and a possible association with Proteus mirabilis. Their findings were that in patients who were rheumatoid factor (RF) seropositive, they also had the highest elevations of antibodies present for Proteus mirabilis and E. coli infections and that patients with erosive disease had higher IgA anti-Proteus titers. The authors call for further investigation of a suspected association for both Proteus mirabilis and E. coli infections in RF-positive RA patients.


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